Regenerative Glycosylation under Nucleophilic Catalysis

Practically all complex carbohydrates have an oligomeric sequence wherein monosaccharide residues are linked via glycosidic linkages.(1) Both simple methods and sophisticated strategies for glycoside synthesis and oligosaccharide assembly exist.(2, 3) However, the complexity of glycosylation reactions(4-7) is responsible for many drawbacks that all current methods experience. In spite of significant progress, chemical glycosylation remains challenging due to the requirement to achieve complete stereocontrol and to suppress side reactions.(8) Among a plethora of leaving groups developed, a vast majority of glycosylations make use of thioglycosides(9-12) and O-trichloroacetimidates (TCAI).(13-15) Our laboratory has also been developing new leaving groups for chemical glycosylation.(16, 17) For instance, we developed S-benzoxazolyl (SBox) donors(18) and more recently introduced O-benzoxazolyl (OBox) imidates,(19) which represent a hybrid structure between SBox and TCAI (Scheme 1), but it is more reactive than either.